.alpha.-Aminoboronic acid derivatives

• US 4,537,773 A
• Filed: 12/05/1983
• Issued: 08/27/1985
• Est. Priority Date: 12/05/1983
• Status: Expired due to Term

• Current Assignee: E. I. du Pont de Nemours and Company (Corteva, Inc.)
• Original Assignee: E. I. du Pont de Nemours and Company (Corteva, Inc.)
• Inventors: Shenvi, Ashokkumar B.
• Primary Examiner(s): Shaver, Paul F.
• Application Number:
  US06/558,361
• Time in Patent Office: 631 Days
• Field of Search: 556/403, 568/6, 260/462 C, 424/185, 424/184
• US Class Current: 514/63
• CPC Class Codes: A01N 55/08 containing boron
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds

Abstract

α-Aminoboronic acids and derivatives of formula ##STR1## are potent, reversible inhibitors of aminopeptidases.

Claims

1. A compound of the formula ##STR33## wherein R is alkyl or --CH₂ R¹ ;

R¹ is --XR², aryl, or aryl substituted with one or more alkyl groups;

R² is --H, alkyl, or --SiR³ R⁴ R⁵ ;

R³, R⁴ and R⁵ are independently alkyl, aryl or aryl substituted with one or more alkoxy groups;

X is O or S;

Y is a moiety derived from a dihydroxy compound comprising at least two hydroxy groups separated by at least two connecting atoms in a chain or ring, said chain or ring comprising carbon atoms and, optionally, a heteroatom which can be N, S, or O; and

HW is a mineral acid, sulfonic acid, alkanoic acid or a perfluoroalkanoic acid.

2. A compound according to claim 1 wherein Y is derived from pinacol, perfluoropinacol, pinanediol, ethylene glycol, diethylene glycol, catachol, 1,2-cyclohexanediol, 1,3-propanediol, 2,3-butanediol, 1,4-butanediol, or diethanolamine.

3. A compound according to claim 2 wherein HW is HCl, HBr, HI, a sulfonic acid, alkanoic acid, or perfluoroalkanoic acid.

4. A compound according to claim 3 wherein R is --CH₃, --CH(CH₃)₂, --CH₂ CH₂ (CH₃)₂, --CH(CH₃)C₂ H₅, or ##STR34##

5. A compound according to claim 4 wherein Y is ##STR35## or --(CH₂)₂ NH(CH₂)₂ --.

6. A compound according to claim 5 wherein HW is CF₃ CO₂ H, CH₃ CO₂ H, HCl or HBr.

7. A compound according to claim 6 wherein R is --CH(CH₃)C₂ H₅ or ##STR36## and HW is CF₃ CO₂ H.

8. A compound according to claim 6 where R is ##STR37## and HW is CF₃ CO₂ H.

9. A compound of formula ##STR38## wherein R and Y are as defined in claim 1, provided that where Y is --CH₂ CH₂ --, R cannot be ##STR39##

10. A compound according to claim 9, wherein Y is derived from pinacol, perfluoropinacol, pinanediol, ethylene glycol, diethylene glycol, catachol, 1,2-cyclohexanediol, 1,3-propanediol, 2,3-butanediol, 1,4-butanediol, or diethanolamine.

11. A compound according to claim 10 wherein R is --CH₃, --CH(CH₃)₂, --CH₂ CH₂ (CH₃)₂, --CH(CH₃)C₂ H₅, or ##STR40##

12. A compound according to claim 11, wherein

Y is ##STR41## or --(CH₂)₂ NH(CH₂)₂ --.

13. A compound of the formula ##STR42## wherein R and Y are as defined in claim 1,

R⁶ through R¹¹ are independently alkyl, aralkyl, aryl, or substituted aryl, provided that, where R⁶ through R¹¹ are each --CH₃ and Y is --CH₂ CH₂ -- or ##STR43##

14. A compound according to claim 13, wherein Y is derived fro pinacol, perfluoropinacol, pinanediol, ethylene glycol, diethylene glycol, catachol, 1,2-cyclohexanediol, 1,3-propanediol, 2,3-butanediol, 1,4-butanediol, or diethanolamine.

15. A compound according to claim 14 wherein R is --CH₃, --CH(CH₃)₂, --CH₂ CH₂ (CH₃)₂, --CH(CH₃)C₂ H₅, or ##STR44##

16. A compound according to claim 15, wherein Y is ##STR45## or --(CH₂)₂ NH(CH₂)₂ --.

17. A compound of the formula ##STR46## wherein R¹² is lower alkyl or benzyl andd Y is as defined in claim 1;

provided that, where Y is --CH₂ CH₂ -- or ##STR47## R¹² cannot be benzyl.

18. A compound of the formula ##STR48## wherein R¹² is lower alkyl or benzyl;

and

Y is as defined in claim 1;

provided that, where Y is --CH₂ CH₂ -- or ##STR49## R¹³ cannot be benzyl.

19. A pharmaceutical composition for potentiating analgesia in a mammal comprising an effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

20. A method of potentiating analgesia in a mammal comprising administering a composition of claim 19.

21. A pharmaceutical composition for potentiating analgesia in a mammal comprising an effective amount of a compound of claim 9 and a pharmaceutically acceptable carrier.

22. A method of potentiating analgesia in a mammal comprising administering a composition of claim 21.